Taste transduction is one of the most sophisticated forms of chemotransduction in animals (Avenet and Lindemann, 1989; Margolskee, 1993; Lindemann, Physiol. Rev. 76:718-766, 1996; Kinnamon et al., Annu. Rev. Physiol. 54:715-731, 1992; and Gilbertson et al., Curr. Opin. Neurobiol. 10: 519-527, 2000). Gustatory signaling is found throughout the animal kingdom, from simple metazoans to the most complex of vertebrates; its main purpose is to provide a reliable signaling response to non-volatile ligands.
Mammals are believed to have five basic types of taste modalities: salty, sour, sweet, umami (the taste of MSG), and bitter. Each of these is thought to be mediated by distinct signaling pathways leading to receptor cell depolarization, generation of a receptor or action potential and release of neurotransmitter and synaptic activity (Roper, ARN, 1989).
In general, the identification of new taste receptors is highly desirable. The identification of a taste receptor provides methods and systems for screening for new tastants, such as the identification of new artificial tastants (sweeteners, sour flavors, salt substitutes, etc.) and for the identification of activity modulators that produce a greater receptor response to specified amounts of a tastant. For example, the ability to modulate activity of the (previously unknown) salt receptor would be highly desirable, e.g., to provide a perception of salt flavor with minimal amounts of salt. This would have clear benefits for patients that suffer from hypertension, obesity, or other diseases that utilize reduced sodium intake as part of patient treatment. The use of sour or other flavor enhancers may also be useful in reducing the amount of sour or other flavoring needed to provoke a sour receptor taste cell response, which may thus be useful as a flavor enhancer.
Relatively recently, the receptors for bitter, sweet and umami were cloned and shown to be encoded by two families of G-protein coupled receptors (Nelson et al., 2000; Nelson et al., 2001; Zhang et al., 2003; Zhao et al., 2003; Mueller et al., 2005). In contrast, most of the molecular components of the sour and salty pathways remain unknown. Electrophysiological studies suggest that sour and salty tastants modulate taste cell function by direct entry of H+ and Na+ ions through specialized membrane channels on the apical surface of the cell. Thus, ion channels selectively expressed in taste receptor cells are likely candidates for mediators of salt and sour tastes. Alternatively, ion channels can function as a final critical signaling component in the activation of taste cells (akin to the role of TRPM5 in sweet, umami and bitter cells; Zhang et al., 2003).
Many other families of cell receptors are also known to function in a variety of signal transduction events associated with cell sensation. For example, the polycystins (e.g., PC1 and PC2, encoded by PKD1 and PKD2, respectively) are integral membrane proteins with large extracellular N termini that are thought to comprise a number of functions, including mechanosensation in renal and nodal cilia (reviewed in Nauli and Zhou 2004 “Polycystins and Mechanosensation in renal and nodal cilia” Bioessays 26.8 844-856 Wiley Periodicals). The polycystins fall into two basic classes of proteins, the PC-1-like proteins, which are receptor-like molecules and the PC-2-like proteins, which are ion channels. Several studies have found overlapping and interdependent roles for these proteins in various systems, particularly in kidney cells.